Effects of insulin-like growth factor I on the renal juxtamedullary microvasculature.
To characterize the effects on the rat renal preglomerular microvasculature of insulin-like growth factor I (IGF-I), experiments were performed using the in vitro blood-perfused juxtamedullary nephron preparation. IGF-I induced a reversible vasodilation of pre- but not postglomerular microvessels in a dose-dependent manner (10(-9)-10(-7) M). The IGF-I-induced vasodilation was similar in all preglomerular vascular segments: interlobular artery, 11.5 +/- 1.2% of control (n = 16); mid-afferent arterioles, 11.6 +/- 1.7% (n = 24); and juxtaglomerular afferent segments, 16.1 +/- 2.8% (n = 19). Renal autoregulatory capacity was not reduced by IGF-I. Pretreatment with the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (10(-4) M) completely inhibited the vasodilatory response to IGF-I. IGF-I induced a rapid increase of NO concentration in intact renal microvessels, monitored by a NO-selective voltametric microelectrode. Pretreatment with the cyclooxygenase inhibitor indomethacin (10(-5) M) not only abrogated the IGF-I-induced dilation, but, moreover, IGF-I elicited a small but significant (approximately 10%) vasoconstriction in all preglomerular vessels. These results indicate that the renal vascular effects of IGF-I involve activation of two endogenous vasodilators (NO and vasodilatory prostaglandins). In addition, IGF-I may also release an undefined vasoconstrictor.
Tönshoff
B
B
Department of Pediatrics, State University of New York at Stony Brook 11794-8661, USA.
Kaskel
F J
FJ
Moore
L C
LC
D000818:Animals; D006706:Homeostasis; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007606:Juxtaglomerular Apparatus / Q000098:blood supply*; D007679:Kidney Medulla / Q000098:blood supply*; D008833:Microcirculation / Q000187:drug effects*; D008839:Microelectrodes; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D009569:Nitric Oxide; D007334:Insulin-Like Growth Factor I; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin